RNA-antibody fusions and their selection
AssigneeThe General Hospital Corporation
InventorsJack W. Szostak, Richard W. Roberts
Life of this patent
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Abstract
Described herein are methods and reagents for the selection of protein molecules that make use of RNA-protein fusions.
Claims12
A molecule comprising a ribonucleic acid covalently bonded through an amide bond to an antibody, wherein said antibody is encoded by said ribonucleic acid.
A molecule comprising a ribonucleic acid covalently bonded to an antibody, said antibody being entirely encoded by said ribonucleic acid.
An RNA-antibody fusion selected by the method comprising the steps of:
- a) providing a population of candidate RNA molecules, each of which comprises a translation initiation sequence and a start codon operably linked to a candidate antibody coding sequence and each of which is operably linked to a peptide acceptor at the 3′ end of said candidate antibody coding sequence;
- b) in vitro or in situ translating said candidate antibody coding sequences to produce a population of candidate RNA-antibody fusions;
- c) contacting said population of candidate RNA-antibody fusions with a target antigen;
- and
- d) selecting an RNA-antibody fusion that binds to said target antigen.
An RNA-antibody fusion selected by the method comprising the steps of:
- a) providing a population of candidate RNA molecules, each of which comprises a translation initiation sequence and a start codon operably linked to a candidate antibody coding sequence and each of which is operably linked to a peptide acceptor at the 3′ end of said candidate antibody coding sequence;
- b) in vitro translating said candidate antibody coding sequences to produce a population of candidate RNA-antibody fusions;
- c) contacting said population of candidate RNA-antibody fusions with a target antigen;
- and
- d) selecting an RNA-antibody fusion that binds to said target antigen.
An RNA-antibody fusion comprising an antibody portion having an altered binding affinity or specificity for a target antigen relative to the binding affinity or specificity of a reference antibody, said RNA-antibody fusion selected by the method comprising the steps of:
- a) producing a population of candidate RNA molecules, each having a candidate antibody coding sequence which differs from said reference antibody coding sequence, said RNA molecules each comprising a translation initiation sequence and a start codon operably linked to said candidate antibody coding sequence and each being operably linked to a peptide acceptor at the 3′ end;
- b) in vitro or in situ translating said candidate antibody coding sequences to produce a population of candidate RNA-antibody fusions;
- c) contacting said population of candidate RNA-antibody fusions with said target antigen;
- and
- d) selecting an RNA-antibody fusion, the antibody portion of which has a binding affinity or specificity for said target antigen that is altered relative to the binding affinity or specificity of said reference antibody for said target antigen.
An RNA-antibody fusion comprising an antibody portion having an altered binding affinity or specificity for a target antigen relative to the binding affinity or specificity of a reference antibody, said RNA-antibody fusion selected by the method comprising the steps of:
- a) producing a population of candidate RNA molecules, each having a candidate antibody coding sequence which differs from said reference antibody coding sequence, said RNA molecules each comprising a translation initiation sequence and a start codon operably linked to said candidate antibody coding sequence and each being operably linked to a peptide acceptor at the 3′ end;
- b) in vitro translating said candidate antibody coding sequences to produce a population of candidate RNA-antibody fusions;
- c) contacting said population of candidate RNA-antibody fusions with said target antigen;
- and
- d) selecting an RNA-antibody fusion, the antibody portion of which has a binding affinity or specificity for said target antigen that is altered relative to the binding affinity or specificity of said reference antibody for said target antigen.
Dependencies are inferred from the claim text.